The following discussion of the prior art is intended to present the invention in an appropriate technical context and allow its significance to be properly appreciated. Unless clearly indicated to the contrary, however, reference to any prior art in this specification should be construed as an admission that such art is widely known or forms part of common general knowledge in the field.
Vilazodone i.e. 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine, and physiologically acceptable salts thereof, are disclosed in U.S. Pat. No. 5,532,241. PCT International Publication No. WO 00/72832 discloses use of Vilazodone in treating certain medical disorders.
U.S. Pat. Nos. 7,834,020 B2 and 7,381,726 B2 disclose fifteen crystalline forms of vilazodone hydrochloride designated as Form-I through Form-XV. They also disclose an amorphous type Form-XVI, which is not a pure amorphous form as it contains characteristic two theta peaks pertaining to crystalline nature of the form. Hence, the art does not provide a pure amorphous form of vilazodone hydrochloride.
The present invention provides substantially pure amorphous form of vilazodone hydrochloride having polymorphic purity greater than 99.9% with no detectable amount of any crystalline forms.
Crystalline solids normally require a significant amount of energy for dissolution due to their highly organized lattice like structures. For example, the energy required for a drug molecule to escape from a crystal is more than from an amorphous or a non-crystalline form. It is known that the amorphous forms in a number of drugs exhibit different dissolution characteristics and in some cases different bioavailability patterns compared to the crystalline form (Econno T., Chem. Pharm. Bull., 1990; 38: 2003-2007). For some therapeutic indications, one bioavailability pattern may be favoured over another.
Amorphous forms of some drugs exhibit much higher bioavailability than the crystalline forms, which leads to the selection of the amorphous form as the final drug substance for pharmaceutical dosage from development. Additionally, the aqueous solubility of crystalline form is lower than of amorphous form in some drugs, which may result in the difference in their in vivo bioavailability. Therefore, it is desirable to have amorphous forms of drugs with high purity to meet the needs of regulatory agencies and also highly reproducible process for their preparation.
In view of the above, it is also desirable to provide an efficient, economical and eco-friendly process for the preparation of highly pure vilazodone hydrochloride in amorphous form.